ArticleJournal of experimental & clinical cancer research : CR2016
The TGFβ-SMAD3 pathway inhibits IL-1α induced interactions between human pancreatic stellate cells and pancreatic carcinoma cells and restricts cancer cell migration.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Therapeutic role of interleukin-1 receptor antagonist in pancreatic diseases: mendelian randomization study.Frontiers in immunology · 2023Pooled it
- Interleukin-1α (IL-1α) in pancreatic ductal adenocarcinoma: implications for immunotherapy and molecular biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Domestication and feedback: bidirectional hijacking in pancreatic ductal adenocarcinoma microenvironment.Frontiers in immunology · 2025Review
- PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy.BMC cancer · 2023Article
- Construction and validation of an aging-related gene signature predicting the prognosis of pancreatic cancer.Frontiers in genetics · 2023Article
- Cinobufacini Inhibits the Development of Pancreatic Cancer Cells through the TGFEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Heterogeneous Pancreatic Stellate Cells Are Powerful Contributors to the Malignant Progression of Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Review
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- Gemcitabine induces Epithelial-to-Mesenchymal Transition in patient-derived pancreatic ductal adenocarcinoma xenografts.American journal of translational research · 2019Article
- Matrine Suppresses Pancreatic Fibrosis by Regulating TGF-β/Smad Signaling in Rats.Yonsei medical journal · 2019Article
- CD25 and TGF-β blockade based on predictive integrated immune ratio inhibits tumor growth in pancreatic cancer.Journal of translational medicine · 2018Article
- Functions of pancreatic stellate cell-derived soluble factors in the microenvironment of pancreatic ductal carcinoma.Oncotarget · 2017Review
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Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe most abundant cells in the extensive desmoplastic stroma of pancreatic adenocarcinomas are the pancreatic stellate cells, which interact with the carcinoma cells and strongly influence the progression of the cancer. Tumor stroma interactions induced by IL-1α/IL-1R1 signaling have been shown to be involved in pancreatic cancer cell migration. TGFβ and its receptors are overexpressed in pancreatic adenocarcinomas. We aimed at exploring TGFβ and IL-1α signaling and cross-talk in the stellate cell cancer cell interactions regulating pancreatic adenocarcinoma cell migration.
methodsHuman pancreatic stellate cells were isolated from surgically resected pancreatic adenocarcinomas and cultured in the presence of TGFβ or pancreatic adenocarcinoma cell lines. The effects of TGFβ were blocked by inhibitors or amplified by silencing the endogenous inhibitor of SMAD signaling, SMAD7. Pancreatic stellate cell responses to IL-1α or to IL-1α-expressing pancreatic adenocarcinoma cells (BxPC-3) were characterized by their ability to stimulate migration of cancer cells in a 2D migration model.
resultsIn pancreatic stellate cells, IL-1R1 expression was found to be down-regulated by TGFβ and blocking of TGFβ signaling re-established the expression. Endogenous inhibition of TGFβ signaling by SMAD7 was found to correlate with the levels of IL-1R1, indicating a regulatory role of SMAD7 in IL-1R1 expression. Pancreatic stellate cells cultured in the presence of IL-1α or in co-cultures with BxPC-3 cells enhanced the migration of cancer cells. This effect was blocked after treatment of the pancreatic stellate cells with TGFβ. Silencing of stellate cell expression of SMAD7 was found to suppress the levels of IL-1R1 and reduce the stimulatory effects of IL-1α, thus inhibiting the capacity of pancreatic stellate cells to induce cancer cell migration.
conclusionsTGFβ signaling suppressed IL-1α mediated pancreatic stellate cell induced carcinoma cell migration. Depletion of SMAD7 upregulated the effects of TGFβ and reduced the expression of IL-1R1, leading to inhibition of IL-1α induced stellate cell enhancement of carcinoma cell migration. SMAD7 might represent a target for inhibition of IL-1α induced tumor stroma interactions.
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